Targeting human telomeric G-quadruplex DNA with curcumin and its synthesized analogues under molecular crowding conditions

The formation of telomeric G-quadruplexes has been shown to inhibit telomerase activity. Indeed, a number of small molecules capable of π-stacking with G-tetrads have shown the ability to inhibit telomerase activity through the stabilization of G-quadruplexes. Curcumin displays a wide spectrum of me...

Full description

Saved in:
Bibliographic Details
Published in:RSC advances 2016-01, Vol.6 (9), p.7474-7487
Main Authors: Jha, Niki S, Mishra, Satyendra, Mamidi, Ashalatha S, Mishra, Archita, Jha, Shailendra K, Surolia, Avadhesha
Format: Article
Language:English
Subjects:
Affinity
Binding
Crowding
Deoxyribonucleic acid
Derivatives
Fungicides
Synthesis (chemistry)
Telomerase
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The formation of telomeric G-quadruplexes has been shown to inhibit telomerase activity. Indeed, a number of small molecules capable of π-stacking with G-tetrads have shown the ability to inhibit telomerase activity through the stabilization of G-quadruplexes. Curcumin displays a wide spectrum of medicinal properties ranging from anti-bacterial, anti-viral, anti-protozoal, anti-fungal and anti-inflammatory to anti-cancer activity. We have investigated the interactions of curcumin and its structural analogues with the human telomeric sequence AG 3 (T 2 AG 3 ) 3 under molecular crowding conditions. Experimental studies indicated the existence of a AG 3 (T 2 AG 3 ) 3 /curcumin complex with binding affinity of 0.72 × 10 6 M −1 under molecular crowding conditions. The results from UV-visible absorption spectroscopy, a fluorescent TO displacement assay, circular dichroism and molecular docking studies, imply that curcumin and their analogues interact with G-quadruplex DNA via groove binding. While other analogs of curcumin studied here bind to G-quadruplexes in a qualitatively similar manner their affinities are relatively lower in comparison to curcumin. The Knoevenagel condensate, a methoxy-benzylidene derivative of curcumin, also exhibited significant binding to G-quadruplex DNA, although with two times decreased affinity. Our study establishes the potential of curcumin as a promising natural product for G-quadruplex specific ligands. The formation of telomeric G-quadruplexes has been shown to inhibit telomerase activity.
ISSN:2046-2069
2046-2069
DOI:10.1039/c5ra17390f